A Phase 2 Randomized Trial of Asleep versus Awake Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease

<b><i>Objective:</i></b> Asleep deep brain stimulation (DBS) for Parkinson’s disease (PD) is being performed more frequently; however, motor outcomes and safety of asleep DBS have never been assessed in a prospective randomized trial. <b><i>Methods:</i></b> We conducted a prospective, randomized, noncomparative trial to assess the motor outcomes of asleep DBS. Leads were implanted in the subthalamic nucleus (STN) according to probabilistic stereotactic coordinates with a surgical robot under O-arm^© imaging guidance under either general anesthesia without microelectrode recordings (MER) (20 patients, asleep group) or local anesthesia with MER and clinical testing (9 patients, awake group). <b><i>Results:</i></b> The mean motor improvement rates on the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-3) between OFF and ON stimulation without medication were 52.3% (95% CI: 45.4–59.2%) in the asleep group and 47.0% (95% CI: 23.8–70.2%) in the awake group, 6 months after surgery. Except for a subcutaneous hematoma, we did not observe any complications related to the surgery. Three patients (33%) in the awake group and 8 in the asleep group (40%) had at least one side effect potentially linked with neurostimulation. <b><i>Conclusions:</i></b> Owing to its randomized design, our study supports the hypothesis that motor outcomes after asleep STN-DBS in PD may be noninferior to the standard awake procedure.

Radial Retinotomies with Endodiathermy for Severe Proliferative Vitreoretinopathy: Short-Term Results

Purpose.Retinal redetachment of silicone oil-filled eyes continues to be a frustrating condition that typically requires retinectomy. We proposed radial retinotomy as a potentially less invasive surgery. Here, we preliminarily explored its feasibility, efficacy, and safety.Methods.Totally 9 eyes of 9 consecutive patients were included in a prospective noncomparative trial. A series of retinotomies were created by endodiathermy in a radial pattern to relax the foreshortened retina. The eye was refilled with fresh silicone oil. The treated eyes were examined via visual acuity (VA) tests, tonometry, slit-lamp microscopy, and fundus photography during a 6-month observation period.Results.The procedure was completed in an average of 28 minutes from silicone oil removal to fresh silicone oil placement. Fundus photography demonstrated that 7 of the 9 eyes (78%) exhibited retinal reattachment. On average, VA was significantly improved within the first 2 weeks (P=0.02) and remained stable for the following 6 months. The change in intraocular pressure was not significant (P=0.76), and no adverse event was observed (0%).Conclusion.Radial retinotomies with endodiathermy were shown to be feasible, effective, and safe in selected cases of inferior contracted retina without vitreous base fibrosis over a 6-month observation period. This trial is registered withNCT02201706.

Effectiveness of a 6-dose regimen of Artemether-Lumefantrine for unsupervised treatment of uncomplicated childhood malaria in Calabar, Nigeria

Background: The six dose regimen of Artemether- Lumefantrine (AL), has high efficacy in clinical trials and is the first -line drug for treating uncomplicated malaria in Nigeria. The complex dosage schedule could militate against its effectiveness.Objective: To assess the effectiveness of AL prescribed under routineoutpatient conditions in the treatment of uncomplicated malaria.Methods: An open label, noncomparative trial to assess the effectivenessof AL in children 6 to 59 months with uncomplicated P. falciparum and parasite density between 1,000 and 250,000/ìL. Enrolled children received 6-dose course of AL (20/120mg tablets). The first dose was administered in the health facility and caregivers were instructed on how to administerthe remaining five doses at home.Results: Of the 1035 screened, 215 eligible children were enrolled and193 completed the study. Twenty two (22) patients withdrew from thestudy (18 were lost to follow-up, 3 violated protocol and 1 withdrewconsent). Adequate clinical and parasitological response (ACPR) was observed in 90.7%; late clinical failure in 7 (3.6%) and late parasitologicalfailure in 11 (5.7%).Conclusion: This study showed high efficacy of AL in treating uncomplicatedP. falciparum malaria in under-fives in Nigeria. Adherence by caregivers to the treatment regimen was quite good and so, should continue to be used in the home setting.Key words: Artemetherlumefantrine, effectiveness, adherence, uncomplicated malaria.

Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma

Purpose We evaluated the efficacy of bevacizumab, alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, open-label, noncomparative trial. Patients and Methods One hundred sixty-seven patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m2 or 125 mg/m2 (with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks. Primary end points were 6-month progression-free survival and objective response rate, as determined by independent radiology review. Secondary end points included safety and overall survival. Results In the bevacizumab-alone and the bevacizumab-plus-irinotecan groups, estimated 6-month progression-free survival rates were 42.6% and 50.3%, respectively; objective response rates were 28.2% and 37.8%, respectively; and median overall survival times were 9.2 months and 8.7 months, respectively. There was a trend for patients who were taking corticosteroids at baseline to take stable or decreasing doses over time. Of the patients treated with bevacizumab alone or bevacizumab plus irinotecan, 46.4% and 65.8%, respectively, experienced grade ≥ 3 adverse events, the most common of which were hypertension (8.3%) and convulsion (6.0%) in the bevacizumab-alone group and convulsion (13.9%), neutropenia (8.9%), and fatigue (8.9%) in the bevacizumab-plus-irinotecan group. Intracranial hemorrhage was noted in two patients (2.4%) in the bevacizumab-alone group (grade 1) and in three patients (3.8%) patients in the bevacizumab-plus-irinotecan group (grades 1, 2, and 4, respectively). Conclusion Bevacizumab, alone or in combination with irinotecan, was well tolerated and active in recurrent glioblastoma.

Clinical Efficacy of Intravenous followed by Oral Azithromycin Monotherapy in Hospitalized Patients with Community-Acquired Pneumonia

ABSTRACT The purpose of this study was to evaluate intravenous (i.v.) azithromycin followed by oral azithromycin as a monotherapeutic regimen for community-acquired pneumonia (CAP). Two trials of i.v. azithromycin used as initial monotherapy in hospitalized CAP patients are summarized. Clinical efficacy is reported from an open-label randomized trial of azithromycin compared to cefuroxime with or without erythromycin. Bacteriologic and clinical efficacy results are also presented from a noncomparative trial of i.v. azithromycin that was designed to give additional clinical experience with a larger number of pathogens. Azithromycin was administered to 414 patients: 202 and 212 in the comparative and noncomparative trials, respectively. The comparator regimen was used as treatment for 201 patients; 105 were treated with cefuroxime alone and 96 were given cefuroxime plus erythromycin. In the comparative trial, clinical outcome data were available for 268 evaluable patients with confirmed CAP at the 10- to 14-day visit, with 106 (77%) of the azithromycin patients cured or improved and 97 (74%) of the comparator patients cured or improved. Mean i.v. treatment duration and mean total treatment duration (i.v. and oral) for the clinically evaluable patients were significantly (P < 0.05) shorter for the azithromycin group (3.6 days for the i.v. group and 8.6 days for the i.v. and oral group) than for the evaluable patients given cefuroxime plus erythromycin (4.0 days for the i.v. group and 10.3 days for the i.v. and oral group). The present comparative study demonstrates that initial therapy with i.v. azithromycin for hospitalized patients with CAP is associated with fewer side effects and is equal in efficacy to a 1993 American Thoracic Society-suggested regimen of cefuroxime plus erythromycin when the erythromycin is deemed necessary by clinicians.